ES2420854T3 - Nuevas fenilpirazinonas como inhibidores de quinasas - Google Patents

Nuevas fenilpirazinonas como inhibidores de quinasas Download PDF

Info

Publication number: ES2420854T3
Authority: ES; Spain
Prior art keywords: alkyl; halogen; optionally substituted; methyl; formula
Prior art date: 2008-07-02
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Active

Application number

ES09772333T

Other languages

English (en)

Spanish (es)

Inventor

Nolan James Dewdney

Yan Lou

Eric Brian Sjogren

Michael Soth

Zachary Kevin Sweeney

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

F Hoffmann La Roche AG

Original Assignee

F Hoffmann La Roche AG

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2008-07-02

Filing date

2009-06-22

Publication date

2013-08-27

2009-06-22 Application filed by F Hoffmann La Roche AG filed Critical F Hoffmann La Roche AG

2013-08-27 Application granted granted Critical

2013-08-27 Publication of ES2420854T3 publication Critical patent/ES2420854T3/es

Status Active legal-status Critical Current

2029-06-22 Anticipated expiration legal-status Critical

Links

229940043355 kinase inhibitor Drugs 0.000 title description 3
239000003757 phosphotransferase inhibitor Substances 0.000 title description 3
SYPKOIOSVWYKHO-UHFFFAOYSA-N 3-phenyl-1h-pyrazin-2-one Chemical class O=C1NC=CN=C1C1=CC=CC=C1 SYPKOIOSVWYKHO-UHFFFAOYSA-N 0.000 title description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 284
229910052736 halogen Inorganic materials 0.000 claims abstract description 174
150000002367 halogens Chemical class 0.000 claims abstract description 174
-1 nitro, amino Chemical group 0.000 claims abstract description 170
150000001875 compounds Chemical class 0.000 claims abstract description 132
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 100
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims abstract description 91
125000001424 substituent group Chemical group 0.000 claims abstract description 52
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 44
125000003118 aryl group Chemical group 0.000 claims abstract description 41
125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 41
125000000217 alkyl group Chemical group 0.000 claims abstract description 40
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 39
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 39
125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims abstract description 26
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 26
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 26
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 18
125000004043 oxo group Chemical group O=* 0.000 claims abstract description 13
125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 12
125000005119 alkyl cycloalkyl group Chemical group 0.000 claims abstract description 12
125000005213 alkyl heteroaryl group Chemical group 0.000 claims abstract description 12
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 12
125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 12
125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims abstract description 12
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims abstract description 10
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 9
125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims abstract description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 107
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 83
238000011282 treatment Methods 0.000 claims description 22
229940124291 BTK inhibitor Drugs 0.000 claims description 21
150000003839 salts Chemical class 0.000 claims description 19
210000003719 b-lymphocyte Anatomy 0.000 claims description 17
230000001363 autoimmune Effects 0.000 claims description 15
239000000546 pharmaceutical excipient Substances 0.000 claims description 15
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 13
125000003545 alkoxy group Chemical group 0.000 claims description 13
239000008194 pharmaceutical composition Substances 0.000 claims description 9
230000001575 pathological effect Effects 0.000 claims description 8
239000003085 diluting agent Substances 0.000 claims description 7
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
230000035755 proliferation Effects 0.000 claims description 4
230000002757 inflammatory effect Effects 0.000 claims description 3
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 137
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 106
239000000203 mixture Substances 0.000 description 93
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 80
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical group C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 78
150000001732 carboxylic acid derivatives Chemical class 0.000 description 65
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 55
125000004356 hydroxy functional group Chemical group O* 0.000 description 51
235000019439 ethyl acetate Nutrition 0.000 description 48
239000000243 solution Substances 0.000 description 48
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 46
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 44
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
125000004076 pyridyl group Chemical group 0.000 description 40
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
239000011541 reaction mixture Substances 0.000 description 33
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 32
238000001819 mass spectrum Methods 0.000 description 30
239000012074 organic phase Substances 0.000 description 27
125000003226 pyrazolyl group Chemical group 0.000 description 27
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
206010003246 arthritis Diseases 0.000 description 25
239000000741 silica gel Substances 0.000 description 24
229910002027 silica gel Inorganic materials 0.000 description 24
238000003818 flash chromatography Methods 0.000 description 23
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
201000010099 disease Diseases 0.000 description 21
230000000694 effects Effects 0.000 description 21
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
239000012267 brine Substances 0.000 description 20
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
239000007787 solid Substances 0.000 description 20
210000004027 cell Anatomy 0.000 description 19
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
239000004480 active ingredient Substances 0.000 description 17
238000003756 stirring Methods 0.000 description 17
125000003373 pyrazinyl group Chemical group 0.000 description 16
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
239000012071 phase Substances 0.000 description 15
208000023275 Autoimmune disease Diseases 0.000 description 14
238000000034 method Methods 0.000 description 14
230000002829 reductive effect Effects 0.000 description 14
239000000725 suspension Substances 0.000 description 14
238000009472 formulation Methods 0.000 description 13
238000002360 preparation method Methods 0.000 description 13
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
239000000843 powder Substances 0.000 description 12
238000000746 purification Methods 0.000 description 12
241001465754 Metazoa Species 0.000 description 11
125000004432 carbon atom Chemical group C* 0.000 description 11
208000035475 disorder Diseases 0.000 description 11
239000004615 ingredient Substances 0.000 description 11
OAPDLBHLMVYMCW-UHFFFAOYSA-M sodium;2-(3-benzoylphenyl)propanoate Chemical compound [Na+].[O-]C(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 OAPDLBHLMVYMCW-UHFFFAOYSA-M 0.000 description 11
239000003826 tablet Substances 0.000 description 11
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
239000002253 acid Substances 0.000 description 10
229910052786 argon Inorganic materials 0.000 description 10
239000000463 material Substances 0.000 description 10
229910052757 nitrogen Inorganic materials 0.000 description 10
239000000758 substrate Substances 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
239000000839 emulsion Substances 0.000 description 9
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
230000002401 inhibitory effect Effects 0.000 description 9
239000011780 sodium chloride Substances 0.000 description 9
229910052938 sodium sulfate Inorganic materials 0.000 description 9
235000011152 sodium sulphate Nutrition 0.000 description 9
238000012360 testing method Methods 0.000 description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
206010061218 Inflammation Diseases 0.000 description 8
108091000080 Phosphotransferase Proteins 0.000 description 8
239000007864 aqueous solution Substances 0.000 description 8
125000004429 atom Chemical group 0.000 description 8
239000002585 base Substances 0.000 description 8
239000000872 buffer Substances 0.000 description 8
239000002775 capsule Substances 0.000 description 8
230000004054 inflammatory process Effects 0.000 description 8
230000005764 inhibitory process Effects 0.000 description 8
239000007788 liquid Substances 0.000 description 8
102000020233 phosphotransferase Human genes 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
241000699670 Mus sp. Species 0.000 description 7
102100029823 Tyrosine-protein kinase BTK Human genes 0.000 description 7
125000002947 alkylene group Chemical group 0.000 description 7
238000003556 assay Methods 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
239000002552 dosage form Substances 0.000 description 7
208000027866 inflammatory disease Diseases 0.000 description 7
239000011734 sodium Substances 0.000 description 7
210000001519 tissue Anatomy 0.000 description 7
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
241000700159 Rattus Species 0.000 description 6
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
229940121363 anti-inflammatory agent Drugs 0.000 description 6
239000002260 anti-inflammatory agent Substances 0.000 description 6
239000003814 drug Substances 0.000 description 6
125000002768 hydroxyalkyl group Chemical group 0.000 description 6
210000000987 immune system Anatomy 0.000 description 6
VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical group C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
229910052943 magnesium sulfate Inorganic materials 0.000 description 6
235000019341 magnesium sulphate Nutrition 0.000 description 6
239000003921 oil Substances 0.000 description 6
235000019198 oils Nutrition 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
108090000765 processed proteins & peptides Proteins 0.000 description 6
239000000047 product Substances 0.000 description 6
KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 5
102000008186 Collagen Human genes 0.000 description 5
108010035532 Collagen Proteins 0.000 description 5
229910021595 Copper(I) iodide Inorganic materials 0.000 description 5
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 5
241000124008 Mammalia Species 0.000 description 5
108010058846 Ovalbumin Proteins 0.000 description 5
230000004913 activation Effects 0.000 description 5
239000013543 active substance Substances 0.000 description 5
208000006673 asthma Diseases 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
229920001436 collagen Polymers 0.000 description 5
239000012141 concentrate Substances 0.000 description 5
235000008504 concentrate Nutrition 0.000 description 5
125000001188 haloalkyl group Chemical group 0.000 description 5
125000005842 heteroatom Chemical group 0.000 description 5
150000002430 hydrocarbons Chemical group 0.000 description 5
208000026278 immune system disease Diseases 0.000 description 5
239000003112 inhibitor Substances 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
210000000265 leukocyte Anatomy 0.000 description 5
210000000056 organ Anatomy 0.000 description 5
229940092253 ovalbumin Drugs 0.000 description 5
125000003884 phenylalkyl group Chemical group 0.000 description 5
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
239000002904 solvent Substances 0.000 description 5
239000000126 substance Substances 0.000 description 5
239000000829 suppository Substances 0.000 description 5
201000000596 systemic lupus erythematosus Diseases 0.000 description 5
239000003981 vehicle Substances 0.000 description 5
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
FUEAPTMAHNCSDV-UHFFFAOYSA-N 1-[2-[(4-methoxyphenyl)methyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]cyclopropane-1-carbaldehyde Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC=C(C3(CC3)C=O)C=C2CC1 FUEAPTMAHNCSDV-UHFFFAOYSA-N 0.000 description 4
BFUATCSAAPJWSW-UHFFFAOYSA-N 2-[2-[(4-methoxyphenyl)methyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]acetamide Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC=C(CC(N)=O)C=C2CC1 BFUATCSAAPJWSW-UHFFFAOYSA-N 0.000 description 4
MJVFFMLAODSYQP-UHFFFAOYSA-N 2-[2-[(4-methoxyphenyl)methyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]acetonitrile Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC=C(CC#N)C=C2CC1 MJVFFMLAODSYQP-UHFFFAOYSA-N 0.000 description 4
OYOLJDQNUMPLJO-UHFFFAOYSA-N 6-[1-(difluoromethyl)cyclopropyl]-2-[(4-methoxyphenyl)methyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC=C(C3(CC3)C(F)F)C=C2CC1 OYOLJDQNUMPLJO-UHFFFAOYSA-N 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
201000010717 Bruton-type agammaglobulinemia Diseases 0.000 description 4
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
206010025323 Lymphomas Diseases 0.000 description 4
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 4
102100040247 Tumor necrosis factor Human genes 0.000 description 4
208000016349 X-linked agammaglobulinemia Diseases 0.000 description 4
229960000583 acetic acid Drugs 0.000 description 4
230000001154 acute effect Effects 0.000 description 4
125000004183 alkoxy alkyl group Chemical group 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
230000003110 anti-inflammatory effect Effects 0.000 description 4
230000006907 apoptotic process Effects 0.000 description 4
239000012131 assay buffer Substances 0.000 description 4
IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 4
125000002619 bicyclic group Chemical group 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
230000001684 chronic effect Effects 0.000 description 4
238000011161 development Methods 0.000 description 4
230000018109 developmental process Effects 0.000 description 4
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
238000011156 evaluation Methods 0.000 description 4
239000001963 growth medium Substances 0.000 description 4
125000004404 heteroalkyl group Chemical group 0.000 description 4
125000000623 heterocyclic group Chemical group 0.000 description 4
229910052739 hydrogen Inorganic materials 0.000 description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
239000008101 lactose Substances 0.000 description 4
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
239000001267 polyvinylpyrrolidone Substances 0.000 description 4
229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 4
238000010992 reflux Methods 0.000 description 4
210000002345 respiratory system Anatomy 0.000 description 4
206010039073 rheumatoid arthritis Diseases 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000003381 stabilizer Substances 0.000 description 4
230000004083 survival effect Effects 0.000 description 4
230000008961 swelling Effects 0.000 description 4
208000024891 symptom Diseases 0.000 description 4
YTZKOQUCBOVLHL-UHFFFAOYSA-N tert-butylbenzene Chemical compound CC(C)(C)C1=CC=CC=C1 YTZKOQUCBOVLHL-UHFFFAOYSA-N 0.000 description 4
239000002562 thickening agent Substances 0.000 description 4
CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 4
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
HUTNOYOBQPAKIA-UHFFFAOYSA-N 1h-pyrazin-2-one Chemical class OC1=CN=CC=N1 HUTNOYOBQPAKIA-UHFFFAOYSA-N 0.000 description 3
NJDNBXHQAJWKLZ-UHFFFAOYSA-N 2-[3-bromo-2-(hydroxymethyl)phenyl]-6-cyclopropyl-3,4-dihydroisoquinolin-1-one Chemical compound OCC1=C(Br)C=CC=C1N1C(=O)C2=CC=C(C3CC3)C=C2CC1 NJDNBXHQAJWKLZ-UHFFFAOYSA-N 0.000 description 3
DSDAKIUDXQGSBU-UHFFFAOYSA-N 2-bromo-6-(6-cyclopropyl-1-oxo-3,4-dihydroisoquinolin-2-yl)benzaldehyde Chemical compound BrC1=CC=CC(N2C(C3=CC=C(C=C3CC2)C2CC2)=O)=C1C=O DSDAKIUDXQGSBU-UHFFFAOYSA-N 0.000 description 3
UVSNKSAYWMIATL-UHFFFAOYSA-N 2-methyl-4-(1-methylcyclopropyl)benzoyl chloride Chemical compound C1=C(C(Cl)=O)C(C)=CC(C2(C)CC2)=C1 UVSNKSAYWMIATL-UHFFFAOYSA-N 0.000 description 3
YWPMKTWUFVOFPL-UHFFFAOYSA-N 3,4-dihydro-2h-isoquinolin-1-one Chemical compound C1=CC=C2C(=O)NCCC2=C1 YWPMKTWUFVOFPL-UHFFFAOYSA-N 0.000 description 3
BQNJLERQQVTUDF-UHFFFAOYSA-N 5-bromo-3-[4-(4-ethylpiperazine-1-carbonyl)anilino]-1-methylpyrazin-2-one Chemical compound C1CN(CC)CCN1C(=O)C(C=C1)=CC=C1NC1=NC(Br)=CN(C)C1=O BQNJLERQQVTUDF-UHFFFAOYSA-N 0.000 description 3
YIMDJFAFGZNRMR-UHFFFAOYSA-N 6-(1-fluoroethenyl)-2-[(4-methoxyphenyl)methyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC=C(C(F)=C)C=C2CC1 YIMDJFAFGZNRMR-UHFFFAOYSA-N 0.000 description 3
JNNONIFIIMARKP-UHFFFAOYSA-N 6-bromo-2-[(4-methoxyphenyl)methyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC=C(Br)C=C2CC1 JNNONIFIIMARKP-UHFFFAOYSA-N 0.000 description 3
FQPKKECSRKYXIZ-UHFFFAOYSA-N 6-bromo-3,4-dihydro-2h-isoquinolin-1-one Chemical compound O=C1NCCC2=CC(Br)=CC=C21 FQPKKECSRKYXIZ-UHFFFAOYSA-N 0.000 description 3
GYFRAGKFZWNDKO-UHFFFAOYSA-N 6-ethenyl-2-[(4-methoxyphenyl)methyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC=C(C=C)C=C2CC1 GYFRAGKFZWNDKO-UHFFFAOYSA-N 0.000 description 3
FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo(3.3.1)nonane Chemical compound C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 3
241000220479 Acacia Species 0.000 description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
208000011231 Crohn disease Diseases 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
208000009386 Experimental Arthritis Diseases 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 3
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 3
235000010643 Leucaena leucocephala Nutrition 0.000 description 3
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 3
239000002202 Polyethylene glycol Substances 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 3
206010047115 Vasculitis Diseases 0.000 description 3
229940022663 acetate Drugs 0.000 description 3
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
239000002671 adjuvant Substances 0.000 description 3
239000000443 aerosol Substances 0.000 description 3
150000001299 aldehydes Chemical class 0.000 description 3
229910000147 aluminium phosphate Inorganic materials 0.000 description 3
235000011114 ammonium hydroxide Nutrition 0.000 description 3
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 3
230000037396 body weight Effects 0.000 description 3
239000011575 calcium Substances 0.000 description 3
229910052791 calcium Inorganic materials 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 3
239000003246 corticosteroid Substances 0.000 description 3
239000006071 cream Substances 0.000 description 3
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
230000002950 deficient Effects 0.000 description 3
PFBUKDPBVNJDEW-UHFFFAOYSA-N dichlorocarbene Chemical group Cl[C]Cl PFBUKDPBVNJDEW-UHFFFAOYSA-N 0.000 description 3
239000002270 dispersing agent Substances 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000000975 dye Substances 0.000 description 3
239000003480 eluent Substances 0.000 description 3
239000003995 emulsifying agent Substances 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
229920000159 gelatin Polymers 0.000 description 3
235000019322 gelatine Nutrition 0.000 description 3
235000011852 gelatine desserts Nutrition 0.000 description 3
210000003630 histaminocyte Anatomy 0.000 description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
239000005457 ice water Substances 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
229960004592 isopropanol Drugs 0.000 description 3
239000006210 lotion Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
230000001404 mediated effect Effects 0.000 description 3
230000008018 melting Effects 0.000 description 3
238000002844 melting Methods 0.000 description 3
229960000485 methotrexate Drugs 0.000 description 3
230000004048 modification Effects 0.000 description 3
238000012986 modification Methods 0.000 description 3
201000006417 multiple sclerosis Diseases 0.000 description 3
150000002825 nitriles Chemical class 0.000 description 3
239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 3
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 3
230000026731 phosphorylation Effects 0.000 description 3
238000006366 phosphorylation reaction Methods 0.000 description 3
239000006187 pill Substances 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
230000009467 reduction Effects 0.000 description 3
230000004044 response Effects 0.000 description 3
238000012770 revaccination Methods 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
210000003491 skin Anatomy 0.000 description 3
230000000638 stimulation Effects 0.000 description 3
239000000375 suspending agent Substances 0.000 description 3
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 3
239000008215 water for injection Substances 0.000 description 3
OQEMWUROKHRRHO-UHFFFAOYSA-N (2,6-dibromophenyl)methyl acetate Chemical compound CC(=O)OCC1=C(Br)C=CC=C1Br OQEMWUROKHRRHO-UHFFFAOYSA-N 0.000 description 2
MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
125000000008 (C1-C10) alkyl group Chemical group 0.000 description 2
UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 2
JRHPOFJADXHYBR-UHFFFAOYSA-N 1-n,2-n-dimethylcyclohexane-1,2-diamine Chemical compound CNC1CCCCC1NC JRHPOFJADXHYBR-UHFFFAOYSA-N 0.000 description 2
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
RKMGAJGJIURJSJ-UHFFFAOYSA-N 2,2,6,6-tetramethylpiperidine Chemical compound CC1(C)CCCC(C)(C)N1 RKMGAJGJIURJSJ-UHFFFAOYSA-N 0.000 description 2
YDYNSAUGVGAOLO-UHFFFAOYSA-N 2,6-dibromobenzaldehyde Chemical compound BrC1=CC=CC(Br)=C1C=O YDYNSAUGVGAOLO-UHFFFAOYSA-N 0.000 description 2
CKAPPACZLLJXGI-UHFFFAOYSA-N 2-(3-bromo-2-ethylphenyl)-6-(1-fluorocyclopropyl)-3,4-dihydroisoquinolin-1-one Chemical compound CCC1=C(Br)C=CC=C1N1C(=O)C2=CC=C(C3(F)CC3)C=C2CC1 CKAPPACZLLJXGI-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
XTXJTIMTSPKONT-UHFFFAOYSA-N 2-methyl-4-(1-methylcyclopropyl)benzoic acid Chemical compound C1=C(C(O)=O)C(C)=CC(C2(C)CC2)=C1 XTXJTIMTSPKONT-UHFFFAOYSA-N 0.000 description 2
HRHMDRXGAPBQOI-UHFFFAOYSA-N 3-(3-bromo-2-methylphenyl)-7-(dimethylamino)-1h-quinolin-4-one Chemical compound C=1C(N(C)C)=CC=C(C2=O)C=1NC=C2C1=CC=CC(Br)=C1C HRHMDRXGAPBQOI-UHFFFAOYSA-N 0.000 description 2
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
JLBJTVDPSNHSKJ-UHFFFAOYSA-N 4-Methylstyrene Chemical compound CC1=CC=C(C=C)C=C1 JLBJTVDPSNHSKJ-UHFFFAOYSA-N 0.000 description 2
XRZGSNXBNZTPEH-UHFFFAOYSA-N 4-bromo-2-(2-bromoethyl)benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(Br)C=C1CCBr XRZGSNXBNZTPEH-UHFFFAOYSA-N 0.000 description 2
125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
AIIDIVNLCSQYJQ-UHFFFAOYSA-N 5-bromo-3-[(1-ethylpyrazol-4-yl)amino]-1-methylpyrazin-2-one Chemical compound C1=NN(CC)C=C1NC1=NC(Br)=CN(C)C1=O AIIDIVNLCSQYJQ-UHFFFAOYSA-N 0.000 description 2
IIJPVOVAVTZFRH-UHFFFAOYSA-N 5-tert-butyl-2,3-dihydroinden-1-one Chemical compound CC(C)(C)C1=CC=C2C(=O)CCC2=C1 IIJPVOVAVTZFRH-UHFFFAOYSA-N 0.000 description 2
KPGBQHZXFFBOTO-UHFFFAOYSA-N 6-(dimethylamino)-2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(N(C)C)=CC=C2C(=O)N1C(C=1)=CC=CC=1B1OC(C)(C)C(C)(C)O1 KPGBQHZXFFBOTO-UHFFFAOYSA-N 0.000 description 2
OWINDRYHDVMGFO-UHFFFAOYSA-N 6-cyclopropyl-3,4-dihydro-2h-isoquinolin-1-one Chemical compound C=1C=C2C(=O)NCCC2=CC=1C1CC1 OWINDRYHDVMGFO-UHFFFAOYSA-N 0.000 description 2
KVSRTYBIFKWHND-UHFFFAOYSA-N 6-tert-butyl-3,4-dihydro-2h-isoquinolin-1-one Chemical compound O=C1NCCC2=CC(C(C)(C)C)=CC=C21 KVSRTYBIFKWHND-UHFFFAOYSA-N 0.000 description 2
108010029445 Agammaglobulinaemia Tyrosine Kinase Proteins 0.000 description 2
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
241000416162 Astragalus gummifer Species 0.000 description 2
208000003950 B-cell lymphoma Diseases 0.000 description 2
208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
239000005711 Benzoic acid Substances 0.000 description 2
FWVGDGRLIBPJQY-UHFFFAOYSA-N BrC=1C(=C(C=CC1)N1C(C2=CC(=CC=C2C=C1)C1(CC1)C)=O)C(O[SiH2]C(C)(C)C)(C)C Chemical compound BrC=1C(=C(C=CC1)N1C(C2=CC(=CC=C2C=C1)C1(CC1)C)=O)C(O[SiH2]C(C)(C)C)(C)C FWVGDGRLIBPJQY-UHFFFAOYSA-N 0.000 description 2
XQIRVNLQLLRDQD-UHFFFAOYSA-N BrC=1C(=C(C=CC1)N1C(C2=CC(=CC=C2CC1O)C1(CC1)C)=O)C(O[SiH2]C(C)(C)C)(C)C Chemical compound BrC=1C(=C(C=CC1)N1C(C2=CC(=CC=C2CC1O)C1(CC1)C)=O)C(O[SiH2]C(C)(C)C)(C)C XQIRVNLQLLRDQD-UHFFFAOYSA-N 0.000 description 2
NXJYVLBPLHTILR-UHFFFAOYSA-N BrC=1C(=C(C=CC1)NC(C1=C(C=C(C=C1)C1(CC1)C)C)=O)C(O[SiH2]C(C)(C)C)(C)C Chemical compound BrC=1C(=C(C=CC1)NC(C1=C(C=C(C=C1)C1(CC1)C)C)=O)C(O[SiH2]C(C)(C)C)(C)C NXJYVLBPLHTILR-UHFFFAOYSA-N 0.000 description 2
239000004255 Butylated hydroxyanisole Substances 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
206010061818 Disease progression Diseases 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
206010018364 Glomerulonephritis Diseases 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
206010020751 Hypersensitivity Diseases 0.000 description 2
206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 2
229910021380 Manganese Chloride Inorganic materials 0.000 description 2
GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 2
208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
201000004681 Psoriasis Diseases 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
206010039710 Scleroderma Diseases 0.000 description 2
206010070834 Sensitisation Diseases 0.000 description 2
229920002684 Sepharose Polymers 0.000 description 2
208000021386 Sjogren Syndrome Diseases 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
229920001615 Tragacanth Polymers 0.000 description 2
108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 2
QQIRAVWVGBTHMJ-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;lithium Chemical compound [Li].C[Si](C)(C)N[Si](C)(C)C QQIRAVWVGBTHMJ-UHFFFAOYSA-N 0.000 description 2
229960001138 acetylsalicylic acid Drugs 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
125000000278 alkyl amino alkyl group Chemical group 0.000 description 2
125000003282 alkyl amino group Chemical group 0.000 description 2
125000003806 alkyl carbonyl amino group Chemical group 0.000 description 2
125000004448 alkyl carbonyl group Chemical group 0.000 description 2
125000004414 alkyl thio group Chemical group 0.000 description 2
208000026935 allergic disease Diseases 0.000 description 2
230000007815 allergy Effects 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
239000005557 antagonist Substances 0.000 description 2
239000002246 antineoplastic agent Substances 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
239000007900 aqueous suspension Substances 0.000 description 2
125000004658 aryl carbonyl amino group Chemical group 0.000 description 2
125000005129 aryl carbonyl group Chemical group 0.000 description 2
201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 2
230000009286 beneficial effect Effects 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
238000010256 biochemical assay Methods 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
239000012455 biphasic mixture Substances 0.000 description 2
239000004305 biphenyl Substances 0.000 description 2
235000010290 biphenyl Nutrition 0.000 description 2
230000005587 bubbling Effects 0.000 description 2
235000019282 butylated hydroxyanisole Nutrition 0.000 description 2
229940043253 butylated hydroxyanisole Drugs 0.000 description 2
CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
229910000024 caesium carbonate Inorganic materials 0.000 description 2
125000002837 carbocyclic group Chemical group 0.000 description 2
229910002092 carbon dioxide Inorganic materials 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
239000000969 carrier Substances 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
230000003034 chemosensitisation Effects 0.000 description 2
229940044683 chemotherapy drug Drugs 0.000 description 2
229940110456 cocoa butter Drugs 0.000 description 2
235000019868 cocoa butter Nutrition 0.000 description 2
239000003086 colorant Substances 0.000 description 2
GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
239000012043 crude product Substances 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
230000006378 damage Effects 0.000 description 2
230000034994 death Effects 0.000 description 2
201000001981 dermatomyositis Diseases 0.000 description 2
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Substances CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
230000005750 disease progression Effects 0.000 description 2
231100000673 dose–response relationship Toxicity 0.000 description 2
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
239000000284 extract Substances 0.000 description 2
239000012091 fetal bovine serum Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
235000019634 flavors Nutrition 0.000 description 2
239000001530 fumaric acid Substances 0.000 description 2
239000000499 gel Substances 0.000 description 2
150000002344 gold compounds Chemical class 0.000 description 2
125000004438 haloalkoxy group Chemical group 0.000 description 2
125000004405 heteroalkoxy group Chemical group 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 2
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
230000001506 immunosuppresive effect Effects 0.000 description 2
230000006872 improvement Effects 0.000 description 2
CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
238000001802 infusion Methods 0.000 description 2
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
230000003993 interaction Effects 0.000 description 2
230000003834 intracellular effect Effects 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
125000000468 ketone group Chemical group 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000000787 lecithin Substances 0.000 description 2
235000010445 lecithin Nutrition 0.000 description 2
229940067606 lecithin Drugs 0.000 description 2
VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 2
229960000681 leflunomide Drugs 0.000 description 2
208000032839 leukemia Diseases 0.000 description 2
239000012669 liquid formulation Substances 0.000 description 2
210000004072 lung Anatomy 0.000 description 2
206010025135 lupus erythematosus Diseases 0.000 description 2
210000004698 lymphocyte Anatomy 0.000 description 2
229910001629 magnesium chloride Inorganic materials 0.000 description 2
239000011565 manganese chloride Substances 0.000 description 2
235000002867 manganese chloride Nutrition 0.000 description 2
239000012528 membrane Substances 0.000 description 2
229940098779 methanesulfonic acid Drugs 0.000 description 2
WBNQUMTUMMNSJW-UHFFFAOYSA-N methyl 2-methyl-4-prop-1-en-2-ylbenzoate Chemical compound COC(=O)C1=CC=C(C(C)=C)C=C1C WBNQUMTUMMNSJW-UHFFFAOYSA-N 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
229960002216 methylparaben Drugs 0.000 description 2
210000001616 monocyte Anatomy 0.000 description 2
TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical compound OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 description 2
OKDQKPLMQBXTNH-UHFFFAOYSA-N n,n-dimethyl-2h-pyridin-1-amine Chemical compound CN(C)N1CC=CC=C1 OKDQKPLMQBXTNH-UHFFFAOYSA-N 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
210000003928 nasal cavity Anatomy 0.000 description 2
239000006199 nebulizer Substances 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
239000002674 ointment Substances 0.000 description 2
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
239000002245 particle Substances 0.000 description 2
239000003961 penetration enhancing agent Substances 0.000 description 2
230000002085 persistent effect Effects 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
235000011056 potassium acetate Nutrition 0.000 description 2
235000011181 potassium carbonates Nutrition 0.000 description 2
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
230000008569 process Effects 0.000 description 2
VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
229960003415 propylparaben Drugs 0.000 description 2
125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 2
PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 2
230000002441 reversible effect Effects 0.000 description 2
150000003873 salicylate salts Chemical group 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
229930195734 saturated hydrocarbon Natural products 0.000 description 2
239000012047 saturated solution Substances 0.000 description 2
230000008313 sensitization Effects 0.000 description 2
230000011664 signaling Effects 0.000 description 2
230000007727 signaling mechanism Effects 0.000 description 2
238000010898 silica gel chromatography Methods 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
229910052717 sulfur Inorganic materials 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
229940124597 therapeutic agent Drugs 0.000 description 2
230000008719 thickening Effects 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
238000011200 topical administration Methods 0.000 description 2
235000010487 tragacanth Nutrition 0.000 description 2
239000000196 tragacanth Substances 0.000 description 2
229940116362 tragacanth Drugs 0.000 description 2
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
229910000404 tripotassium phosphate Inorganic materials 0.000 description 2
235000019798 tripotassium phosphate Nutrition 0.000 description 2
238000011144 upstream manufacturing Methods 0.000 description 2
229910052720 vanadium Inorganic materials 0.000 description 2
229910052725 zinc Inorganic materials 0.000 description 2
239000011701 zinc Substances 0.000 description 2
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
HIPQGHZXOAYZNX-UHFFFAOYSA-N (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) acetate Chemical compound C(C)(=O)OB1OC(C(O1)(C)C)(C)C HIPQGHZXOAYZNX-UHFFFAOYSA-N 0.000 description 1
125000000027 (C1-C10) alkoxy group Chemical group 0.000 description 1
125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 1
MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 1
PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
FROIOESJRJZRFO-UHFFFAOYSA-N 1,3-dibromo-2-ethylbenzene Chemical compound CCC1=C(Br)C=CC=C1Br FROIOESJRJZRFO-UHFFFAOYSA-N 0.000 description 1
OCSKCBIGEMSDIS-UHFFFAOYSA-N 1,3-dibromo-2-methylbenzene Chemical compound CC1=C(Br)C=CC=C1Br OCSKCBIGEMSDIS-UHFFFAOYSA-N 0.000 description 1
KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
NFTWWHSKWXOTLL-UHFFFAOYSA-N 1,4-dimethylpiperazin-2-one Chemical compound CN1CCN(C)C(=O)C1 NFTWWHSKWXOTLL-UHFFFAOYSA-N 0.000 description 1
MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
PGEXZJNDEJAPFW-UHFFFAOYSA-N 1-[2-[(4-methoxyphenyl)methyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]cyclopropane-1-carbonitrile Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC=C(C3(CC3)C#N)C=C2CC1 PGEXZJNDEJAPFW-UHFFFAOYSA-N 0.000 description 1
ZDWCLHJHUMKCQS-UHFFFAOYSA-N 1-bromo-3-(2-bromoethyl)benzene Chemical compound BrCCC1=CC=CC(Br)=C1 ZDWCLHJHUMKCQS-UHFFFAOYSA-N 0.000 description 1
ZQXCQTAELHSNAT-UHFFFAOYSA-N 1-chloro-3-nitro-5-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(Cl)=CC(C(F)(F)F)=C1 ZQXCQTAELHSNAT-UHFFFAOYSA-N 0.000 description 1
125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 1
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
AXINVSXSGNSVLV-UHFFFAOYSA-N 1h-pyrazol-4-amine Chemical compound NC=1C=NNC=1 AXINVSXSGNSVLV-UHFFFAOYSA-N 0.000 description 1
YRAJNWYBUCUFBD-UHFFFAOYSA-N 2,2,6,6-tetramethylheptane-3,5-dione Chemical compound CC(C)(C)C(=O)CC(=O)C(C)(C)C YRAJNWYBUCUFBD-UHFFFAOYSA-N 0.000 description 1
RZQQXRVPPOOCQR-UHFFFAOYSA-N 2,3-dihydro-1,3,4-oxadiazole Chemical compound C1NN=CO1 RZQQXRVPPOOCQR-UHFFFAOYSA-N 0.000 description 1
XWWYZFUBBJHKSP-UHFFFAOYSA-N 2,3-dihydro-1h-quinazolin-4-one Chemical compound C1=CC=C2C(=O)NCNC2=C1 XWWYZFUBBJHKSP-UHFFFAOYSA-N 0.000 description 1
HNVIQLPOGUDBSU-UHFFFAOYSA-N 2,6-dimethylmorpholine Chemical compound CC1CNCC(C)O1 HNVIQLPOGUDBSU-UHFFFAOYSA-N 0.000 description 1
RIIFNHGSHYYVFH-UHFFFAOYSA-N 2-(3-bromo-2-methylphenyl)-6-(dimethylamino)isoquinolin-1-one Chemical compound C=1C(N(C)C)=CC=C(C2=O)C=1C=CN2C1=CC=CC(Br)=C1C RIIFNHGSHYYVFH-UHFFFAOYSA-N 0.000 description 1
XRTBUMVELCDXFF-UHFFFAOYSA-N 2-(3-bromophenyl)-6-(dimethylamino)-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(N(C)C)=CC=C2C(=O)N1C1=CC=CC(Br)=C1 XRTBUMVELCDXFF-UHFFFAOYSA-N 0.000 description 1
RDVWFRYQBMQRHA-UHFFFAOYSA-N 2-[3-[6-[4-(4-acetylpiperazine-1-carbonyl)anilino]-4-methyl-5-oxopyrazin-2-yl]-2-(hydroxymethyl)phenyl]-6-cyclopropyl-3,4-dihydroisoquinolin-1-one Chemical compound C1CN(C(=O)C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC(C=2C(=C(N3C(C4=CC=C(C=C4CC3)C3CC3)=O)C=CC=2)CO)=CN(C)C1=O RDVWFRYQBMQRHA-UHFFFAOYSA-N 0.000 description 1
ZLLMMPOKOTYPNB-UHFFFAOYSA-N 2-[3-[6-[4-[bis(2-hydroxyethyl)amino]anilino]-4-methyl-5-oxopyrazin-2-yl]-2-(hydroxymethyl)phenyl]-6-(dimethylamino)-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(N(C)C)=CC=C2C(=O)N1C(C=1CO)=CC=CC=1C(N=1)=CN(C)C(=O)C=1NC1=CC=C(N(CCO)CCO)C=C1 ZLLMMPOKOTYPNB-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
125000003635 2-dimethylaminoethoxy group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 description 1
UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
LWTXVDVQISPSEP-UHFFFAOYSA-N 2-methyl-4-(1-methylcyclopropyl)benzoic acid methyl 2-methyl-4-(1-methylcyclopropyl)benzoate Chemical compound COC(C1=C(C=C(C=C1)C1(CC1)C)C)=O.CC1=C(C(=O)O)C=CC(=C1)C1(CC1)C LWTXVDVQISPSEP-UHFFFAOYSA-N 0.000 description 1
MLMQPDHYNJCQAO-UHFFFAOYSA-N 3,3-dimethylbutyric acid Chemical compound CC(C)(C)CC(O)=O MLMQPDHYNJCQAO-UHFFFAOYSA-N 0.000 description 1
TZOYXRMEFDYWDQ-UHFFFAOYSA-N 3,4-dihydro-1h-quinolin-2-one Chemical compound C1=CC=C2NC(=O)CCC2=C1 TZOYXRMEFDYWDQ-UHFFFAOYSA-N 0.000 description 1
VSCYCJOVRGSJBT-UHFFFAOYSA-N 3,4-dihydro-2h-1$l^{6},2-benzothiazine 1,1-dioxide Chemical compound C1=CC=C2S(=O)(=O)NCCC2=C1 VSCYCJOVRGSJBT-UHFFFAOYSA-N 0.000 description 1
YRLORWPBJZEGBX-UHFFFAOYSA-N 3,4-dihydro-2h-1,4-benzoxazine Chemical compound C1=CC=C2NCCOC2=C1 YRLORWPBJZEGBX-UHFFFAOYSA-N 0.000 description 1
LNVJQIHAUHVGEV-UHFFFAOYSA-N 3,5-dibromo-1-methylpyrazin-2-one Chemical compound CN1C=C(Br)N=C(Br)C1=O LNVJQIHAUHVGEV-UHFFFAOYSA-N 0.000 description 1
XLZYKTYMLBOINK-UHFFFAOYSA-N 3-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C(=O)C=2C=CC(O)=CC=2)=C1 XLZYKTYMLBOINK-UHFFFAOYSA-N 0.000 description 1
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
INUNLMUAPJVRME-UHFFFAOYSA-N 3-chloropropanoyl chloride Chemical compound ClCCC(Cl)=O INUNLMUAPJVRME-UHFFFAOYSA-N 0.000 description 1
ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
HHSBHVJQXZLIRW-UHFFFAOYSA-N 3-n,3-n-dimethylbenzene-1,3-diamine Chemical compound CN(C)C1=CC=CC(N)=C1 HHSBHVJQXZLIRW-UHFFFAOYSA-N 0.000 description 1
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
ZWFNJCFUXXFOCJ-UHFFFAOYSA-N 4-[(6-bromo-4-methyl-3-oxopyrazin-2-yl)amino]benzaldehyde Chemical compound O=C1N(C)C=C(Br)N=C1NC1=CC=C(C=O)C=C1 ZWFNJCFUXXFOCJ-UHFFFAOYSA-N 0.000 description 1
XXXYITSQJSYMTR-UHFFFAOYSA-N 4-[[6-[3-(6-cyclopropyl-1-oxo-3,4-dihydroisoquinolin-2-yl)-2-(hydroxymethyl)phenyl]-4-methyl-3-oxopyrazin-2-yl]amino]-n,n-bis(2-hydroxyethyl)benzamide Chemical compound O=C1N(C)C=C(C=2C(=C(N3C(C4=CC=C(C=C4CC3)C3CC3)=O)C=CC=2)CO)N=C1NC1=CC=C(C(=O)N(CCO)CCO)C=C1 XXXYITSQJSYMTR-UHFFFAOYSA-N 0.000 description 1
SOWKNEKJJNMGSO-UHFFFAOYSA-N 4-[[6-[3-(6-cyclopropyl-1-oxo-3,4-dihydroisoquinolin-2-yl)-2-(hydroxymethyl)phenyl]-4-methyl-3-oxopyrazin-2-yl]amino]-n,n-bis(2-methoxyethyl)benzamide Chemical compound C1=CC(C(=O)N(CCOC)CCOC)=CC=C1NC1=NC(C=2C(=C(N3C(C4=CC=C(C=C4CC3)C3CC3)=O)C=CC=2)CO)=CN(C)C1=O SOWKNEKJJNMGSO-UHFFFAOYSA-N 0.000 description 1
HTERSEBROKZYHZ-UHFFFAOYSA-N 4-[[6-[3-(6-cyclopropyl-1-oxo-3,4-dihydroisoquinolin-2-yl)-2-(hydroxymethyl)phenyl]-4-methyl-3-oxopyrazin-2-yl]amino]-n-(2-methoxyethyl)benzamide Chemical compound C1=CC(C(=O)NCCOC)=CC=C1NC1=NC(C=2C(=C(N3C(C4=CC=C(C=C4CC3)C3CC3)=O)C=CC=2)CO)=CN(C)C1=O HTERSEBROKZYHZ-UHFFFAOYSA-N 0.000 description 1
RJWBTWIBUIGANW-UHFFFAOYSA-N 4-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-N 0.000 description 1
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
UXQBJUPWCFEZLR-UHFFFAOYSA-N 5-bromo-1-methyl-3-[4-(morpholin-4-ylmethyl)anilino]pyrazin-2-one Chemical compound O=C1N(C)C=C(Br)N=C1NC(C=C1)=CC=C1CN1CCOCC1 UXQBJUPWCFEZLR-UHFFFAOYSA-N 0.000 description 1
KSONICAHAPRCMV-UHFFFAOYSA-N 5-bromo-2,3-dihydroinden-1-one Chemical compound BrC1=CC=C2C(=O)CCC2=C1 KSONICAHAPRCMV-UHFFFAOYSA-N 0.000 description 1
PUOQZPWTNMJDRO-UHFFFAOYSA-N 5-bromo-3-[4-(hydroxymethyl)anilino]-1-methylpyrazin-2-one Chemical compound O=C1N(C)C=C(Br)N=C1NC1=CC=C(CO)C=C1 PUOQZPWTNMJDRO-UHFFFAOYSA-N 0.000 description 1
BMGVFXUMEAYBAO-UHFFFAOYSA-N 5-phenyl-1h-pyrazin-2-one Chemical class N1C(=O)C=NC(C=2C=CC=CC=2)=C1 BMGVFXUMEAYBAO-UHFFFAOYSA-N 0.000 description 1
RWFAQYWIBBVEBY-UHFFFAOYSA-N 5-phenyl-1h-pyridin-2-one Chemical group N1C(=O)C=CC(C=2C=CC=CC=2)=C1 RWFAQYWIBBVEBY-UHFFFAOYSA-N 0.000 description 1
QHZBHDMCPJYYLF-UHFFFAOYSA-N 6-(1-fluorocyclopropyl)-2-[(4-methoxyphenyl)methyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC=C(C3(F)CC3)C=C2CC1 QHZBHDMCPJYYLF-UHFFFAOYSA-N 0.000 description 1
QZSNRUANHYSIBH-UHFFFAOYSA-N 6-(1-fluorocyclopropyl)-3,4-dihydro-2h-isoquinolin-1-one Chemical compound C=1C=C2C(=O)NCCC2=CC=1C1(F)CC1 QZSNRUANHYSIBH-UHFFFAOYSA-N 0.000 description 1
UESBHTDJDYFXJJ-UHFFFAOYSA-N 6-(dimethylamino)-2-[2-(hydroxymethyl)-3-[4-methyl-5-oxo-6-[4-(piperidin-1-ylmethyl)anilino]pyrazin-2-yl]phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(N(C)C)=CC=C2C(=O)N1C(C=1CO)=CC=CC=1C(N=1)=CN(C)C(=O)C=1NC(C=C1)=CC=C1CN1CCCCC1 UESBHTDJDYFXJJ-UHFFFAOYSA-N 0.000 description 1
HNRQDGLETZJBSY-UHFFFAOYSA-N 6-(dimethylamino)-2-[2-(hydroxymethyl)-3-[4-methyl-6-[4-(morpholine-4-carbonyl)anilino]-5-oxopyrazin-2-yl]phenyl]isoquinolin-1-one Chemical compound C=1C(N(C)C)=CC=C(C2=O)C=1C=CN2C(C=1CO)=CC=CC=1C(N=1)=CN(C)C(=O)C=1NC(C=C1)=CC=C1C(=O)N1CCOCC1 HNRQDGLETZJBSY-UHFFFAOYSA-N 0.000 description 1
NMHLQBLBKDQTTK-UHFFFAOYSA-N 6-(dimethylamino)-2-[2-(hydroxymethyl)-3-[6-[4-(4-hydroxypiperidine-1-carbonyl)anilino]-4-methyl-5-oxopyrazin-2-yl]phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(N(C)C)=CC=C2C(=O)N1C(C=1CO)=CC=CC=1C(N=1)=CN(C)C(=O)C=1NC(C=C1)=CC=C1C(=O)N1CCC(O)CC1 NMHLQBLBKDQTTK-UHFFFAOYSA-N 0.000 description 1
PBKQKKWUKRHTSK-UHFFFAOYSA-N 6-(dimethylamino)-2-[3-[6-(3-fluoro-4-morpholin-4-ylanilino)-4-methyl-5-oxopyrazin-2-yl]-2-(hydroxymethyl)phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(N(C)C)=CC=C2C(=O)N1C(C=1CO)=CC=CC=1C(N=1)=CN(C)C(=O)C=1NC(C=C1F)=CC=C1N1CCOCC1 PBKQKKWUKRHTSK-UHFFFAOYSA-N 0.000 description 1
IYTWDZRBPBJIJO-UHFFFAOYSA-N 6-(dimethylamino)-2-[3-[6-[4-(2-hydroxyethoxy)anilino]-4-methyl-5-oxopyrazin-2-yl]-2-(hydroxymethyl)phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC(N(C)C)=CC=C2C(=O)N1C(C=1CO)=CC=CC=1C(N=1)=CN(C)C(=O)C=1NC1=CC=C(OCCO)C=C1 IYTWDZRBPBJIJO-UHFFFAOYSA-N 0.000 description 1
LQAHENLGZAGBOB-UHFFFAOYSA-N 6-(dimethylamino)-2-[3-[6-[4-(4-ethoxypiperidine-1-carbonyl)anilino]-4-methyl-5-oxopyrazin-2-yl]-2-(hydroxymethyl)phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1CC(OCC)CCN1C(=O)C(C=C1)=CC=C1NC1=NC(C=2C(=C(N3C(C4=CC=C(C=C4CC3)N(C)C)=O)C=CC=2)CO)=CN(C)C1=O LQAHENLGZAGBOB-UHFFFAOYSA-N 0.000 description 1
WTTHDMCWDJFQFR-UHFFFAOYSA-N 6-(dimethylamino)-2h-isoquinolin-1-one Chemical compound C1=CNC(=O)C=2C1=CC(N(C)C)=CC=2 WTTHDMCWDJFQFR-UHFFFAOYSA-N 0.000 description 1
YMVYDDCPVLLCNR-UHFFFAOYSA-N 6-(dimethylamino)-3,4-dihydro-2h-isoquinolin-1-one Chemical compound O=C1NCCC2=CC(N(C)C)=CC=C21 YMVYDDCPVLLCNR-UHFFFAOYSA-N 0.000 description 1
ACZXUKYXRLKXTA-UHFFFAOYSA-N 6-bromo-3,4-dihydro-2H-isoquinolin-1-one methanesulfonic acid Chemical compound CS(=O)(=O)O.BrC=1C=C2CCNC(C2=CC1)=O ACZXUKYXRLKXTA-UHFFFAOYSA-N 0.000 description 1
FBQGISUSVUTGHE-UHFFFAOYSA-N 6-cyclopropyl-2-[2-(hydroxymethyl)-3-[4-methyl-5-oxo-6-[(1-propan-2-ylpyrazol-4-yl)amino]pyrazin-2-yl]phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1=NN(C(C)C)C=C1NC1=NC(C=2C(=C(N3C(C4=CC=C(C=C4CC3)C3CC3)=O)C=CC=2)CO)=CN(C)C1=O FBQGISUSVUTGHE-UHFFFAOYSA-N 0.000 description 1
MOGAZXINYBQKLS-UHFFFAOYSA-N 6-cyclopropyl-2-[2-(hydroxymethyl)-3-[4-methyl-5-oxo-6-[4-(4-propan-2-ylpiperazine-1-carbonyl)anilino]pyrazin-2-yl]phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1CN(C(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC(C=2C(=C(N3C(C4=CC=C(C=C4CC3)C3CC3)=O)C=CC=2)CO)=CN(C)C1=O MOGAZXINYBQKLS-UHFFFAOYSA-N 0.000 description 1
NCZDDAFSXNMKBY-UHFFFAOYSA-N 6-cyclopropyl-2-[2-(hydroxymethyl)-3-[4-methyl-6-[4-(2-morpholin-4-yl-2-oxoethyl)anilino]-5-oxopyrazin-2-yl]phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound O=C1N(C)C=C(C=2C(=C(N3C(C4=CC=C(C=C4CC3)C3CC3)=O)C=CC=2)CO)N=C1NC(C=C1)=CC=C1CC(=O)N1CCOCC1 NCZDDAFSXNMKBY-UHFFFAOYSA-N 0.000 description 1
XWXWLYZRDRPSCA-UHFFFAOYSA-N 6-cyclopropyl-2-[2-(hydroxymethyl)-3-[4-methyl-6-[4-(4-methyl-1,4-diazepane-1-carbonyl)anilino]-5-oxopyrazin-2-yl]phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1CN(C)CCCN1C(=O)C(C=C1)=CC=C1NC1=NC(C=2C(=C(N3C(C4=CC=C(C=C4CC3)C3CC3)=O)C=CC=2)CO)=CN(C)C1=O XWXWLYZRDRPSCA-UHFFFAOYSA-N 0.000 description 1
ZJTJHUPMVASYCP-UHFFFAOYSA-N 6-cyclopropyl-2-[2-(hydroxymethyl)-3-[4-methyl-6-[4-(morpholine-4-carbonyl)-3-nitroanilino]-5-oxopyrazin-2-yl]phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound O=C1N(C)C=C(C=2C(=C(N3C(C4=CC=C(C=C4CC3)C3CC3)=O)C=CC=2)CO)N=C1NC(C=C1[N+]([O-])=O)=CC=C1C(=O)N1CCOCC1 ZJTJHUPMVASYCP-UHFFFAOYSA-N 0.000 description 1
MFKDTRWJKHSMJO-UHFFFAOYSA-N 6-cyclopropyl-2-[2-(hydroxymethyl)-3-[6-[4-[4-(methoxymethyl)piperidine-1-carbonyl]anilino]-4-methyl-5-oxopyrazin-2-yl]phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1CC(COC)CCN1C(=O)C(C=C1)=CC=C1NC1=NC(C=2C(=C(N3C(C4=CC=C(C=C4CC3)C3CC3)=O)C=CC=2)CO)=CN(C)C1=O MFKDTRWJKHSMJO-UHFFFAOYSA-N 0.000 description 1
RFNYFSZDECDAEG-MUUNZHRXSA-N 6-cyclopropyl-2-[3-[6-[4-[(3r)-3-ethoxypyrrolidine-1-carbonyl]anilino]-4-methyl-5-oxopyrazin-2-yl]-2-(hydroxymethyl)phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1[C@H](OCC)CCN1C(=O)C(C=C1)=CC=C1NC1=NC(C=2C(=C(N3C(C4=CC=C(C=C4CC3)C3CC3)=O)C=CC=2)CO)=CN(C)C1=O RFNYFSZDECDAEG-MUUNZHRXSA-N 0.000 description 1
RFNYFSZDECDAEG-NDEPHWFRSA-N 6-cyclopropyl-2-[3-[6-[4-[(3s)-3-ethoxypyrrolidine-1-carbonyl]anilino]-4-methyl-5-oxopyrazin-2-yl]-2-(hydroxymethyl)phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1[C@@H](OCC)CCN1C(=O)C(C=C1)=CC=C1NC1=NC(C=2C(=C(N3C(C4=CC=C(C=C4CC3)C3CC3)=O)C=CC=2)CO)=CN(C)C1=O RFNYFSZDECDAEG-NDEPHWFRSA-N 0.000 description 1
URTXAGSWRBFMRJ-UHFFFAOYSA-N 6-tert-butyl-2-[2-(hydroxymethyl)-3-[4-methyl-6-[4-(morpholine-4-carbonyl)anilino]-5-oxopyrazin-2-yl]phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound O=C1N(C)C=C(C=2C(=C(N3C(C4=CC=C(C=C4CC3)C(C)(C)C)=O)C=CC=2)CO)N=C1NC(C=C1)=CC=C1C(=O)N1CCOCC1 URTXAGSWRBFMRJ-UHFFFAOYSA-N 0.000 description 1
STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
AMKGKYQBASDDJB-UHFFFAOYSA-N 9$l^{2}-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1[B]2 AMKGKYQBASDDJB-UHFFFAOYSA-N 0.000 description 1
XGWFJBFNAQHLEF-UHFFFAOYSA-N 9-anthroic acid Chemical compound C1=CC=C2C(C(=O)O)=C(C=CC=C3)C3=CC2=C1 XGWFJBFNAQHLEF-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
208000026872 Addison Disease Diseases 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
201000001320 Atherosclerosis Diseases 0.000 description 1
208000023345 Autoimmune Diseases of the Nervous System Diseases 0.000 description 1
206010003827 Autoimmune hepatitis Diseases 0.000 description 1
206010050245 Autoimmune thrombocytopenia Diseases 0.000 description 1
208000004736 B-Cell Leukemia Diseases 0.000 description 1
208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
208000009137 Behcet syndrome Diseases 0.000 description 1
208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
208000019838 Blood disease Diseases 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
POZDMDJYIFRRHH-UHFFFAOYSA-N BrC=1C(=C(C=CC1)N)C(O[SiH2]C(C)(C)C)(C)C Chemical compound BrC=1C(=C(C=CC1)N)C(O[SiH2]C(C)(C)C)(C)C POZDMDJYIFRRHH-UHFFFAOYSA-N 0.000 description 1
208000011691 Burkitt lymphomas Diseases 0.000 description 1
GNZGPKSZBDYVQG-UHFFFAOYSA-N CC(=O)OC(C)(C)CC1=CC2=C(C=C1)C(=O)N(CC2)CC3=CC=C(C=C3)OC Chemical compound CC(=O)OC(C)(C)CC1=CC2=C(C=C1)C(=O)N(CC2)CC3=CC=C(C=C3)OC GNZGPKSZBDYVQG-UHFFFAOYSA-N 0.000 description 1
FDGXCIHPRJEQOJ-UHFFFAOYSA-N CC(C)(C)c1ccc2C(=O)CCc2c1.CC(C)(C)c1ccc(cc1)C(=O)CCCl Chemical compound CC(C)(C)c1ccc2C(=O)CCc2c1.CC(C)(C)c1ccc(cc1)C(=O)CCCl FDGXCIHPRJEQOJ-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
102000011727 Caspases Human genes 0.000 description 1
108010076667 Caspases Proteins 0.000 description 1
241000498849 Chlamydiales Species 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
206010009900 Colitis ulcerative Diseases 0.000 description 1
102000000503 Collagen Type II Human genes 0.000 description 1
108010041390 Collagen Type II Proteins 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
229920002785 Croscarmellose sodium Polymers 0.000 description 1
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
108010036949 Cyclosporine Proteins 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
229940124087 DNA topoisomerase II inhibitor Drugs 0.000 description 1
WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
201000004624 Dermatitis Diseases 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
239000004338 Dichlorodifluoromethane Substances 0.000 description 1
229940117937 Dihydrofolate reductase inhibitor Drugs 0.000 description 1
229940083266 Dihydroorotate dehydrogenase inhibitor Drugs 0.000 description 1
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
208000007465 Giant cell arteritis Diseases 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
206010018634 Gouty Arthritis Diseases 0.000 description 1
208000009329 Graft vs Host Disease Diseases 0.000 description 1
206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
208000003807 Graves Disease Diseases 0.000 description 1
208000015023 Graves' disease Diseases 0.000 description 1
208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
239000007821 HATU Substances 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
239000012981 Hank's balanced salt solution Substances 0.000 description 1
208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
208000017604 Hodgkin disease Diseases 0.000 description 1
208000021519 Hodgkin lymphoma Diseases 0.000 description 1
208000010747 Hodgkins lymphoma Diseases 0.000 description 1
241000282412 Homo Species 0.000 description 1
101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
108060003951 Immunoglobulin Proteins 0.000 description 1
102000004877 Insulin Human genes 0.000 description 1
108090001061 Insulin Proteins 0.000 description 1
UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
208000003456 Juvenile Arthritis Diseases 0.000 description 1
229930194542 Keto Natural products 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
229930182816 L-glutamine Natural products 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
208000016604 Lyme disease Diseases 0.000 description 1
208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
MQHWFIOJQSCFNM-UHFFFAOYSA-L Magnesium salicylate Chemical compound [Mg+2].OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O MQHWFIOJQSCFNM-UHFFFAOYSA-L 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
206010049567 Miller Fisher syndrome Diseases 0.000 description 1
229920000881 Modified starch Polymers 0.000 description 1
TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Natural products OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 description 1
208000034578 Multiple myelomas Diseases 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
ZRKWMRDKSOPRRS-UHFFFAOYSA-N N-Methyl-N-nitrosourea Chemical compound O=NN(C)C(N)=O ZRKWMRDKSOPRRS-UHFFFAOYSA-N 0.000 description 1
OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-N 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
239000002033 PVDF binder Substances 0.000 description 1
229930012538 Paclitaxel Natural products 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
208000037273 Pathologic Processes Diseases 0.000 description 1
229910002666 PdCl2 Inorganic materials 0.000 description 1
201000011152 Pemphigus Diseases 0.000 description 1
208000031845 Pernicious anaemia Diseases 0.000 description 1
206010035226 Plasma cell myeloma Diseases 0.000 description 1
239000004743 Polypropylene Substances 0.000 description 1
229920001214 Polysorbate 60 Polymers 0.000 description 1
208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
208000012654 Primary biliary cholangitis Diseases 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 1
108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 1
102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
201000001263 Psoriatic Arthritis Diseases 0.000 description 1
208000036824 Psoriatic arthropathy Diseases 0.000 description 1
206010037394 Pulmonary haemorrhage Diseases 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
239000012980 RPMI-1640 medium Substances 0.000 description 1
208000025747 Rheumatic disease Diseases 0.000 description 1
206010040070 Septic Shock Diseases 0.000 description 1
102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 1
HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
210000001744 T-lymphocyte Anatomy 0.000 description 1
239000012317 TBTU Substances 0.000 description 1
QYTDEUPAUMOIOP-UHFFFAOYSA-N TEMPO Chemical group CC1(C)CCCC(C)(C)N1[O] QYTDEUPAUMOIOP-UHFFFAOYSA-N 0.000 description 1
QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
239000000317 Topoisomerase II Inhibitor Substances 0.000 description 1
102100040403 Tumor necrosis factor receptor superfamily member 6 Human genes 0.000 description 1
206010054094 Tumour necrosis Diseases 0.000 description 1
201000006704 Ulcerative Colitis Diseases 0.000 description 1
JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
206010047642 Vitiligo Diseases 0.000 description 1
208000027418 Wounds and injury Diseases 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
DDQXWRNBDDQDBD-UHFFFAOYSA-N [2-bromo-6-(6-tert-butyl-1-oxo-3,4-dihydroisoquinolin-2-yl)phenyl]methyl acetate Chemical compound CC(=O)OCC1=C(Br)C=CC=C1N1C(=O)C2=CC=C(C(C)(C)C)C=C2CC1 DDQXWRNBDDQDBD-UHFFFAOYSA-N 0.000 description 1
IBSIIIUWAGFSET-UHFFFAOYSA-N [2-bromo-6-[6-(dimethylamino)-1-oxo-3,4-dihydroisoquinolin-2-yl]phenyl]methyl acetate Chemical compound C1CC2=CC(N(C)C)=CC=C2C(=O)N1C1=CC=CC(Br)=C1COC(C)=O IBSIIIUWAGFSET-UHFFFAOYSA-N 0.000 description 1
NAEFBXSLJRQIMV-UHFFFAOYSA-N [2-bromo-6-[6-(dimethylamino)-1-oxoisoquinolin-2-yl]phenyl]methyl acetate Chemical compound C=1C(N(C)C)=CC=C(C2=O)C=1C=CN2C1=CC=CC(Br)=C1COC(C)=O NAEFBXSLJRQIMV-UHFFFAOYSA-N 0.000 description 1
230000001594 aberrant effect Effects 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
230000005856 abnormality Effects 0.000 description 1
IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
UUIFVXZZFPBDKX-UHFFFAOYSA-N acetyl acetate [2-bromo-6-(6-cyclopropyl-1-oxo-3,4-dihydroisoquinolin-2-yl)phenyl]methyl acetate Chemical compound C(C)(=O)OC(C)=O.BrC1=C(COC(C)=O)C(=CC=C1)N1C(C2=CC=C(C=C2CC1)C1CC1)=O UUIFVXZZFPBDKX-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000009471 action Effects 0.000 description 1
208000025368 adrenal gland disease Diseases 0.000 description 1
229910001413 alkali metal ion Inorganic materials 0.000 description 1
229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
125000004457 alkyl amino carbonyl group Chemical group 0.000 description 1
125000004471 alkyl aminosulfonyl group Chemical group 0.000 description 1
125000005115 alkyl carbamoyl group Chemical group 0.000 description 1
125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
125000004656 alkyl sulfonylamino group Chemical group 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
125000005466 alkylenyl group Chemical group 0.000 description 1
230000000172 allergic effect Effects 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
229940037003 alum Drugs 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
150000001409 amidines Chemical class 0.000 description 1
125000004103 aminoalkyl group Chemical group 0.000 description 1
235000012538 ammonium bicarbonate Nutrition 0.000 description 1
239000001099 ammonium carbonate Substances 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
230000002424 anti-apoptotic effect Effects 0.000 description 1
239000000427 antigen Substances 0.000 description 1
108091007433 antigens Proteins 0.000 description 1
102000036639 antigens Human genes 0.000 description 1
239000008135 aqueous vehicle Substances 0.000 description 1
239000012300 argon atmosphere Substances 0.000 description 1
235000019568 aromas Nutrition 0.000 description 1
230000002917 arthritic effect Effects 0.000 description 1
235000021311 artificial sweeteners Nutrition 0.000 description 1
125000005100 aryl amino carbonyl group Chemical group 0.000 description 1
125000005141 aryl amino sulfonyl group Chemical group 0.000 description 1
125000005116 aryl carbamoyl group Chemical group 0.000 description 1
125000004657 aryl sulfonyl amino group Chemical group 0.000 description 1
125000004391 aryl sulfonyl group Chemical group 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
230000002238 attenuated effect Effects 0.000 description 1
AUJRCFUBUPVWSZ-XTZHGVARSA-M auranofin Chemical compound CCP(CC)(CC)=[Au]S[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O AUJRCFUBUPVWSZ-XTZHGVARSA-M 0.000 description 1
229960005207 auranofin Drugs 0.000 description 1
208000035362 autoimmune disorder of the nervous system Diseases 0.000 description 1
201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
208000037979 autoimmune inflammatory disease Diseases 0.000 description 1
201000004339 autoimmune neuropathy Diseases 0.000 description 1
208000006424 autoimmune oophoritis Diseases 0.000 description 1
201000004982 autoimmune uveitis Diseases 0.000 description 1
229960002170 azathioprine Drugs 0.000 description 1
LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
125000002393 azetidinyl group Chemical group 0.000 description 1
125000003828 azulenyl group Chemical group 0.000 description 1
108010056708 bcr-abl Fusion Proteins Proteins 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
NEJSGLFAMBAJAH-UHFFFAOYSA-N benzyl 2-(3-bromo-2-methylphenyl)acetate Chemical compound CC1=C(Br)C=CC=C1CC(=O)OCC1=CC=CC=C1 NEJSGLFAMBAJAH-UHFFFAOYSA-N 0.000 description 1
GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
239000003124 biologic agent Substances 0.000 description 1
AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
210000001185 bone marrow Anatomy 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229910052792 caesium Inorganic materials 0.000 description 1
TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
235000011148 calcium chloride Nutrition 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
229940127093 camptothecin Drugs 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229960004424 carbon dioxide Drugs 0.000 description 1
ZFTFAPZRGNKQPU-UHFFFAOYSA-L carboxylato carbonate Chemical compound [O-]C(=O)OC([O-])=O ZFTFAPZRGNKQPU-UHFFFAOYSA-L 0.000 description 1
229960000590 celecoxib Drugs 0.000 description 1
RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
230000011712 cell development Effects 0.000 description 1
230000004663 cell proliferation Effects 0.000 description 1
230000005754 cellular signaling Effects 0.000 description 1
230000008859 change Effects 0.000 description 1
150000005829 chemical entities Chemical class 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960002688 choline salicylate Drugs 0.000 description 1
210000000349 chromosome Anatomy 0.000 description 1
208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
229960001265 ciclosporin Drugs 0.000 description 1
235000013985 cinnamic acid Nutrition 0.000 description 1
229930016911 cinnamic acid Natural products 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
229940039116 combination diclofenac Drugs 0.000 description 1
238000002648 combination therapy Methods 0.000 description 1
230000001010 compromised effect Effects 0.000 description 1
238000004590 computer program Methods 0.000 description 1
210000002808 connective tissue Anatomy 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000010949 copper Substances 0.000 description 1
229960001334 corticosteroids Drugs 0.000 description 1
229940111134 coxibs Drugs 0.000 description 1
229960001681 croscarmellose sodium Drugs 0.000 description 1
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
239000013058 crude material Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
229960004397 cyclophosphamide Drugs 0.000 description 1
WLVKDFJTYKELLQ-UHFFFAOYSA-N cyclopropylboronic acid Chemical compound OB(O)C1CC1 WLVKDFJTYKELLQ-UHFFFAOYSA-N 0.000 description 1
229930182912 cyclosporin Natural products 0.000 description 1
STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
210000004207 dermis Anatomy 0.000 description 1
230000000368 destabilizing effect Effects 0.000 description 1
229960003957 dexamethasone Drugs 0.000 description 1
UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
125000004985 dialkyl amino alkyl group Chemical group 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
125000005117 dialkylcarbamoyl group Chemical group 0.000 description 1
WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
229940042935 dichlorodifluoromethane Drugs 0.000 description 1
229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
KPHWPUGNDIVLNH-UHFFFAOYSA-M diclofenac sodium Chemical compound [Na+].[O-]C(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl KPHWPUGNDIVLNH-UHFFFAOYSA-M 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 1
230000004069 differentiation Effects 0.000 description 1
HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 1
229960000616 diflunisal Drugs 0.000 description 1
239000003166 dihydrofolate reductase inhibitor Substances 0.000 description 1
239000003363 dihydroorotate dehydrogenase inhibitor Substances 0.000 description 1
NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 1
USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical group C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 1
KZTYYGOKRVBIMI-UHFFFAOYSA-N diphenyl sulfone Chemical group C=1C=CC=CC=1S(=O)(=O)C1=CC=CC=C1 KZTYYGOKRVBIMI-UHFFFAOYSA-N 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
238000009826 distribution Methods 0.000 description 1
VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
229960002224 eculizumab Drugs 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
210000003372 endocrine gland Anatomy 0.000 description 1
125000002587 enol group Chemical group 0.000 description 1
150000002085 enols Chemical class 0.000 description 1
HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
238000009505 enteric coating Methods 0.000 description 1
239000002532 enzyme inhibitor Substances 0.000 description 1
210000003979 eosinophil Anatomy 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
125000006232 ethoxy propyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
GGHUQGCBDAXMRS-UHFFFAOYSA-N ethyl 2-(3-bromo-2-methylphenyl)-3-[3-(dimethylamino)anilino]prop-2-enoate Chemical compound C=1C=CC(Br)=C(C)C=1C(C(=O)OCC)=CNC1=CC=CC(N(C)C)=C1 GGHUQGCBDAXMRS-UHFFFAOYSA-N 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
229960005293 etodolac Drugs 0.000 description 1
XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 description 1
VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
229960005420 etoposide Drugs 0.000 description 1
229960004945 etoricoxib Drugs 0.000 description 1
MNJVRJDLRVPLFE-UHFFFAOYSA-N etoricoxib Chemical compound C1=NC(C)=CC=C1C1=NC=C(Cl)C=C1C1=CC=C(S(C)(=O)=O)C=C1 MNJVRJDLRVPLFE-UHFFFAOYSA-N 0.000 description 1
230000005284 excitation Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000013265 extended release Methods 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
230000001605 fetal effect Effects 0.000 description 1
238000013100 final test Methods 0.000 description 1
239000012530 fluid Substances 0.000 description 1
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229960002390 flurbiprofen Drugs 0.000 description 1
SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
239000006260 foam Substances 0.000 description 1
WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
230000006650 fundamental cellular process Effects 0.000 description 1
239000007789 gas Substances 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
239000003349 gelling agent Substances 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
239000008103 glucose Substances 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
229940015045 gold sodium thiomalate Drugs 0.000 description 1
208000024908 graft versus host disease Diseases 0.000 description 1
239000008187 granular material Substances 0.000 description 1
235000021552 granulated sugar Nutrition 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
210000002768 hair cell Anatomy 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
230000036541 health Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
208000014951 hematologic disease Diseases 0.000 description 1
208000018706 hematopoietic system disease Diseases 0.000 description 1
230000002949 hemolytic effect Effects 0.000 description 1
208000031209 hemophilic arthropathy Diseases 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004634 hexahydroazepinyl group Chemical group N1(CCCCCC1)* 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
239000003906 humectant Substances 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
XXSMGPRMXLTPCZ-UHFFFAOYSA-N hydroxychloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CCO)CC)=CC=NC2=C1 XXSMGPRMXLTPCZ-UHFFFAOYSA-N 0.000 description 1
229960004171 hydroxychloroquine Drugs 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
229960001680 ibuprofen Drugs 0.000 description 1
125000002636 imidazolinyl group Chemical group 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
230000028993 immune response Effects 0.000 description 1
230000036039 immunity Effects 0.000 description 1
230000003053 immunization Effects 0.000 description 1
238000002649 immunization Methods 0.000 description 1
102000018358 immunoglobulin Human genes 0.000 description 1
229960003444 immunosuppressant agent Drugs 0.000 description 1
239000003018 immunosuppressive agent Substances 0.000 description 1
230000002637 immunotoxin Effects 0.000 description 1
229940051026 immunotoxin Drugs 0.000 description 1
239000002596 immunotoxin Substances 0.000 description 1
231100000608 immunotoxin Toxicity 0.000 description 1
239000007943 implant Substances 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
229960000905 indomethacin Drugs 0.000 description 1
230000004968 inflammatory condition Effects 0.000 description 1
229960000598 infliximab Drugs 0.000 description 1
208000014674 injury Diseases 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
208000028774 intestinal disease Diseases 0.000 description 1
210000000936 intestine Anatomy 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
208000002551 irritable bowel syndrome Diseases 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
125000003965 isoxazolidinyl group Chemical group 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
229960000994 lumiracoxib Drugs 0.000 description 1
KHPKQFYUPIUARC-UHFFFAOYSA-N lumiracoxib Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=CC=C1Cl KHPKQFYUPIUARC-UHFFFAOYSA-N 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
235000014380 magnesium carbonate Nutrition 0.000 description 1
229940072082 magnesium salicylate Drugs 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
230000003211 malignant effect Effects 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
230000035800 maturation Effects 0.000 description 1
210000003519 mature b lymphocyte Anatomy 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
238000002483 medication Methods 0.000 description 1
229960001924 melphalan Drugs 0.000 description 1
SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
229910021645 metal ion Inorganic materials 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
WVWZECQNFWFVFW-UHFFFAOYSA-N methyl 2-methylbenzoate Chemical compound COC(=O)C1=CC=CC=C1C WVWZECQNFWFVFW-UHFFFAOYSA-N 0.000 description 1
CYEXEOXALMJXDI-UHFFFAOYSA-N methyl 4-bromo-2-methylbenzoate Chemical compound COC(=O)C1=CC=C(Br)C=C1C CYEXEOXALMJXDI-UHFFFAOYSA-N 0.000 description 1
OJLOPKGSLYJEMD-URPKTTJQSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(1e)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC OJLOPKGSLYJEMD-URPKTTJQSA-N 0.000 description 1
WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
229960004584 methylprednisolone Drugs 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
230000005012 migration Effects 0.000 description 1
238000013508 migration Methods 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
229960005249 misoprostol Drugs 0.000 description 1
235000019426 modified starch Nutrition 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
230000000877 morphologic effect Effects 0.000 description 1
238000010172 mouse model Methods 0.000 description 1
230000003387 muscular Effects 0.000 description 1
230000035772 mutation Effects 0.000 description 1
206010028417 myasthenia gravis Diseases 0.000 description 1
RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
229960004866 mycophenolate mofetil Drugs 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
229960002009 naproxen Drugs 0.000 description 1
CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
229960003940 naproxen sodium Drugs 0.000 description 1
CDBRNDSHEYLDJV-FVGYRXGTSA-M naproxen sodium Chemical compound [Na+].C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CDBRNDSHEYLDJV-FVGYRXGTSA-M 0.000 description 1
229920001206 natural gum Polymers 0.000 description 1
235000021096 natural sweeteners Nutrition 0.000 description 1
230000007837 negative regulation of B cell activation Effects 0.000 description 1
230000021766 negative regulation of B cell proliferation Effects 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
210000000653 nervous system Anatomy 0.000 description 1
210000000440 neutrophil Anatomy 0.000 description 1
239000002547 new drug Substances 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
239000008008 oral excipient Substances 0.000 description 1
201000005737 orchitis Diseases 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
150000002895 organic esters Chemical class 0.000 description 1
201000008482 osteoarthritis Diseases 0.000 description 1
229960002739 oxaprozin Drugs 0.000 description 1
OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 description 1
125000000160 oxazolidinyl group Chemical group 0.000 description 1
125000003566 oxetanyl group Chemical group 0.000 description 1
229960001592 paclitaxel Drugs 0.000 description 1
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
239000006072 paste Substances 0.000 description 1
230000009054 pathological process Effects 0.000 description 1
230000007170 pathology Effects 0.000 description 1
239000001814 pectin Substances 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
201000001976 pemphigus vulgaris Diseases 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
229950003203 pexelizumab Drugs 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
230000003285 pharmacodynamic effect Effects 0.000 description 1
125000005561 phenanthryl group Chemical group 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
IJAPPYDYQCXOEF-UHFFFAOYSA-N phthalazin-1(2H)-one Chemical compound C1=CC=C2C(=O)NN=CC2=C1 IJAPPYDYQCXOEF-UHFFFAOYSA-N 0.000 description 1
229960002702 piroxicam Drugs 0.000 description 1
QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
239000011505 plaster Substances 0.000 description 1
229920001983 poloxamer Polymers 0.000 description 1
229920000747 poly(lactic acid) Polymers 0.000 description 1
229940057838 polyethylene glycol 4000 Drugs 0.000 description 1
239000004626 polylactic acid Substances 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
208000005987 polymyositis Diseases 0.000 description 1
229920000137 polyphosphoric acid Polymers 0.000 description 1
229920001155 polypropylene Polymers 0.000 description 1
229920002981 polyvinylidene fluoride Polymers 0.000 description 1
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
229910000343 potassium bisulfate Inorganic materials 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
238000011533 pre-incubation Methods 0.000 description 1
239000002243 precursor Substances 0.000 description 1
229960005205 prednisolone Drugs 0.000 description 1
OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
JDOZJEUDSLGTLU-VWUMJDOOSA-N prednisolone phosphate Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COP(O)(O)=O)[C@@H]4[C@@H]3CCC2=C1 JDOZJEUDSLGTLU-VWUMJDOOSA-N 0.000 description 1
229960002943 prednisolone sodium phosphate Drugs 0.000 description 1
229960004618 prednisone Drugs 0.000 description 1
XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
230000003449 preventive effect Effects 0.000 description 1
230000000861 pro-apoptotic effect Effects 0.000 description 1
DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 1
229960003081 probenecid Drugs 0.000 description 1
230000000770 proinflammatory effect Effects 0.000 description 1
WCONKKYQBKPMNZ-UHFFFAOYSA-N prop-1-en-2-ylboronic acid Chemical compound CC(=C)B(O)O WCONKKYQBKPMNZ-UHFFFAOYSA-N 0.000 description 1
239000003380 propellant Substances 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
239000000376 reactant Substances 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000008844 regulatory mechanism Effects 0.000 description 1
230000002787 reinforcement Effects 0.000 description 1
230000027425 release of sequestered calcium ion into cytosol Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
230000000552 rheumatic effect Effects 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
230000036303 septic shock Effects 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
229920002379 silicone rubber Polymers 0.000 description 1
239000004945 silicone rubber Substances 0.000 description 1
238000009097 single-agent therapy Methods 0.000 description 1
208000017520 skin disease Diseases 0.000 description 1
239000002002 slurry Substances 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229940054269 sodium pyruvate Drugs 0.000 description 1
229960004025 sodium salicylate Drugs 0.000 description 1
AGHLUVOCTHWMJV-UHFFFAOYSA-J sodium;gold(3+);2-sulfanylbutanedioate Chemical compound [Na+].[Au+3].[O-]C(=O)CC(S)C([O-])=O.[O-]C(=O)CC(S)C([O-])=O AGHLUVOCTHWMJV-UHFFFAOYSA-J 0.000 description 1
239000012439 solid excipient Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
241000894007 species Species 0.000 description 1
239000007921 spray Substances 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
239000012086 standard solution Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 1
CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
229960001940 sulfasalazine Drugs 0.000 description 1
NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
229960000894 sulindac Drugs 0.000 description 1
MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
230000001629 suppression Effects 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
230000001360 synchronised effect Effects 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
230000009897 systematic effect Effects 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
229960001967 tacrolimus Drugs 0.000 description 1
QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
230000008685 targeting Effects 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
206010043207 temporal arteritis Diseases 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
230000003582 thrombocytopenic effect Effects 0.000 description 1
QGUALMNFRILWRA-UHFFFAOYSA-M tolmetin sodium Chemical compound [Na+].C1=CC(C)=CC=C1C(=O)C1=CC=C(CC([O-])=O)N1C QGUALMNFRILWRA-UHFFFAOYSA-M 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
229960000303 topotecan Drugs 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
210000003437 trachea Anatomy 0.000 description 1
230000037317 transdermal delivery Effects 0.000 description 1
230000005945 translocation Effects 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
229940062627 tribasic potassium phosphate Drugs 0.000 description 1
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
229940086542 triethylamine Drugs 0.000 description 1
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
125000001874 trioxidanyl group Chemical group [*]OOO[H] 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
229960002004 valdecoxib Drugs 0.000 description 1
LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
229940099259 vaseline Drugs 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
239000011345 viscous material Substances 0.000 description 1
235000012431 wafers Nutrition 0.000 description 1
UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Immunology (AREA)
Diabetes (AREA)
Dermatology (AREA)
Hematology (AREA)
Neurology (AREA)
Orthopedic Medicine & Surgery (AREA)
Pulmonology (AREA)
Physical Education & Sports Medicine (AREA)
Rheumatology (AREA)
Transplantation (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Pain & Pain Management (AREA)
Obesity (AREA)
Endocrinology (AREA)
Emergency Medicine (AREA)
Gastroenterology & Hepatology (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

ES09772333T 2008-07-02 2009-06-22 Nuevas fenilpirazinonas como inhibidores de quinasas Active ES2420854T3 (es)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US7751008P	2008-07-02	2008-07-02
US77510		2008-07-02
PCT/EP2009/057707 WO2010000633A1 (fr)	2008-07-02	2009-06-22	Nouvelles phénylpyrazinones en tant qu’inhibiteurs de kinases

Publications (1)

Publication Number	Publication Date
ES2420854T3 true ES2420854T3 (es)	2013-08-27

Family

ID=40940244

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ES09772333T Active ES2420854T3 (es)	2008-07-02	2009-06-22	Nuevas fenilpirazinonas como inhibidores de quinasas

Country Status (24)

Country	Link
US (1)	US8536166B2 (fr)
EP (1)	EP2300459B1 (fr)
JP (1)	JP5490789B2 (fr)
KR (2)	KR101320763B1 (fr)
CN (1)	CN102083819B (fr)
AR (1)	AR072545A1 (fr)
AU (1)	AU2009265813B2 (fr)
BR (1)	BRPI0913879A2 (fr)
CA (1)	CA2728683C (fr)
CL (1)	CL2010001608A1 (fr)
CY (1)	CY1114223T1 (fr)
DK (1)	DK2300459T3 (fr)
ES (1)	ES2420854T3 (fr)
HR (1)	HRP20130698T1 (fr)
IL (1)	IL209729A0 (fr)
MX (1)	MX2010013478A (fr)
PE (1)	PE20110164A1 (fr)
PL (1)	PL2300459T3 (fr)
PT (1)	PT2300459E (fr)
RU (1)	RU2507202C2 (fr)
SI (1)	SI2300459T1 (fr)
TW (1)	TWI401083B (fr)
WO (1)	WO2010000633A1 (fr)
ZA (1)	ZA201008808B (fr)

Families Citing this family (45)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US8299077B2 (en)	2009-03-02	2012-10-30	Roche Palo Alto Llc	Inhibitors of Bruton's tyrosine kinase
SG175287A1 (en) *	2009-04-24	2011-11-28	Hoffmann La Roche	Inhibitors of bruton's tyrosine kinase
EP2566869B1 (fr) *	2010-05-07	2016-03-02	Gilead Connecticut, Inc.	Composés de pyridone et d'aza-pyridone et leurs procédés d'utilisation
AR082590A1 (es)	2010-08-12	2012-12-19	Hoffmann La Roche	Inhibidores de la tirosina-quinasa de bruton
CN106220614B (zh) *	2010-09-01	2019-07-16	吉利德康涅狄格有限公司	吡啶酮/吡嗪酮、其制备方法及使用方法
CN103732596B (zh)	2011-07-08	2016-06-01	诺华股份有限公司	吡咯并嘧啶衍生物
SG11201401993RA (en) *	2011-11-03	2014-05-29	Hoffmann La Roche	Alkylated piperazine compounds as inhibitors of btk activity
HK1205111A1 (en)	2011-11-03	2015-12-11	霍夫曼-拉罗奇有限公司	8-fluorophthalazin-1 (2h) - one compounds as inhibitors of btk activity
ES2552514T3 (es)	2011-11-03	2015-11-30	Hoffmann-La Roche Ag	Compuestos bicíclicos de piperazina
UA111756C2 (uk)	2011-11-03	2016-06-10	Ф. Хоффманн-Ля Рош Аг	Сполуки гетероарилпіридону та азапіридону як інгібітори тирозинкінази брутона
WO2013148603A1 (fr)	2012-03-27	2013-10-03	Takeda Pharmaceutical Company Limited	Dérivés de cinnoline en tant qu'en tant qu'inhibiteurs de la btk
CA2869954C (fr)	2012-04-20	2023-01-03	Advinus Therapeutics Limited	Composes heterobicycliques substitues, compositions et applications medicales associees aux etats medicaux associes a la modulation de l'activite de la tyrosine kinase de bruton
EP2895473A1 (fr) *	2012-09-13	2015-07-22	F. Hoffmann-La Roche AG	Inhibiteurs de la tyrosine kinase de bruton
WO2014108820A1 (fr) *	2013-01-08	2014-07-17	Aurigene Discovery Technologies Limited	Dérivés de 2-pyrazinone substitués en tant qu'inhibiteurs de kinase
WO2014125410A1 (fr) *	2013-02-12	2014-08-21	Aurigene Discovery Technologies Limited	Dérivés hétérocycliques n-substitués à titre d'inhibiteurs de kinases
JP6089124B2 (ja)	2013-03-05	2017-03-01	エフ．ホフマン−ラロシュアーゲーＦ．Ｈｏｆｆｍａｎｎ−ＬａＲｏｃｈｅＡｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ	ブルトン型チロシンキナーゼの阻害薬
JO3377B1 (ar)	2013-03-11	2019-03-13	Takeda Pharmaceuticals Co	مشتقات بيريدينيل وبيريدينيل مندمج
SMT201700160T1 (it)	2013-04-25	2017-05-08	Beigene Ltd	Composti eterociclici fusi come inibitori di protein chinasi
CN104177338B (zh) *	2013-05-22	2018-04-03	南京勇山生物科技有限公司	一类布鲁顿激酶抑制剂
CN104211703B (zh) *	2013-05-30	2018-04-03	南京勇山生物科技有限公司	一类作为布鲁顿激酶抑制剂的稠杂环化合物
CN110698481B (zh) *	2013-07-03	2023-02-28	豪夫迈·罗氏有限公司	杂芳基吡啶酮和氮杂-吡啶酮酰胺化合物
KR101742550B1 (ko) *	2013-07-26	2017-06-01	카나 바이오사이언스, 인코포레이션	신규 트리아진 유도체
MX2016001304A (es)	2013-07-30	2016-04-07	Gilead Connecticut Inc	Polimorfo de inhibidores de syk.
PT3027171T (pt)	2013-07-30	2020-06-18	Gilead Connecticut Inc	Formulação de inibidores da syk
ES2792183T3 (es)	2013-09-13	2020-11-10	Beigene Switzerland Gmbh	Anticuerpos anti-PD1 y su uso como productos terapéuticos y de diagnóstico
US9512084B2 (en)	2013-11-29	2016-12-06	Novartis Ag	Amino pyrimidine derivatives
KR101813830B1 (ko)	2013-12-05	2017-12-29	에프. 호프만-라 로슈 아게	친전자성 작용기를 갖는 헤테로아릴 피리돈 및 아자-피리돈 화합물
TWI735853B (zh)	2013-12-23	2021-08-11	美商克洛諾斯生技有限公司	脾酪胺酸激酶抑制劑
CN106604742B (zh)	2014-07-03	2019-01-11	百济神州有限公司	抗pd-l1抗体及其作为治疗剂及诊断剂的用途
EP3042903B1 (fr) *	2015-01-06	2019-08-14	Impetis Biosciences Ltd.	Composés hétéro-bicycliques substitués, compositions et leurs applications médicales
ES2876974T3 (es)	2015-04-07	2021-11-15	Novartis Ag	Combinación de terapia con receptor de antígeno quimérico y derivados de amino pirimidina
AU2017240609B2 (en)	2016-03-31	2021-07-15	Takeda Pharmaceutical Company Limited	Isoquinolinyl triazolone complexes
CN109475536B (zh)	2016-07-05	2022-05-27	百济神州有限公司	用于治疗癌症的PD-l拮抗剂和RAF抑制剂的组合
WO2018033853A2 (fr)	2016-08-16	2018-02-22	Beigene, Ltd.	Forme cristalline de (s)-7-(1-acryloylpipéridin-4-yl)-2-(4-phénoxyphényle)-4,5,6,7-tétra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide, sa préparation et ses utilisations
PT3500299T (pt)	2016-08-19	2024-02-21	Beigene Switzerland Gmbh	Combinação de zanubrutinib com um anticorpo anti-cd20 ou anti-pd-1 para utilização no tratamento do cancro
MA46285A (fr)	2016-09-19	2019-07-31	Mei Pharma Inc	Polythérapie
WO2018098275A1 (fr) *	2016-11-22	2018-05-31	Dana-Farber Cancer Institute, Inc.	Dégradation de la tyrosine kinase de bruton (btk) par conjugaison d'inhibiteurs de btk avec un ligand de la ligase e3 et procédés d'utilisation
CN110461847B (zh)	2017-01-25	2022-06-07	百济神州有限公司	(S)-7-(1-(丁-2-炔酰基)哌啶-4-基)-2-(4-苯氧基苯基)-4,5,6,7-四氢吡唑并[1,5-a]嘧啶-3-甲酰胺的结晶形式、其制备及用途
TW202515616A (zh)	2017-06-26	2025-04-16	英屬開曼群島商百濟神州有限公司	抗pd-1抗體或其抗原結合片段在製備治療用於患有肝細胞癌(hcc)之藥物的用途
CN110997677A (zh)	2017-08-12	2020-04-10	百济神州有限公司	具有改进的双重选择性的Btk抑制剂
CN115028640A (zh)	2017-08-25	2022-09-09	吉利德科学公司	Syk抑制剂的多晶型物
WO2019108795A1 (fr)	2017-11-29	2019-06-06	Beigene Switzerland Gmbh	Traitement de lymphomes à cellules b indolentes ou agressives au moyen d'une combinaison comprenant des inhibiteurs de btk
KR20210131372A (ko)	2019-02-22	2021-11-02	크로노스 바이오, 인코포레이티드	Syk 억제제로서의 축합된 피라진의 고체 형태
WO2020249001A1 (fr)	2019-06-10	2020-12-17	百济神州瑞士有限责任公司	Comprimé solide pour voie orale comprenant un inhibiteur de tyrosine kinase de bruton et son procédé de préparation
US11786531B1 (en)	2022-06-08	2023-10-17	Beigene Switzerland Gmbh	Methods of treating B-cell proliferative disorder

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2323771A1 (fr) *	1998-03-14	1999-09-23	Byk Gulden Lomberg Chemische Fabrik Gmbh	Inhibiteurs de pde iii/iv a base de phtalazinones
BR0113930A (pt) *	2000-09-15	2003-06-24	Anormed Inc	Compostos heterocìclicos de ligação aos receptores de quimiocina
DE602004005881T2 (de) *	2003-10-14	2008-01-17	Pharmacia Corp.	Substituierte pyrazinonverbindungen zur behandlung von entzündungen
CA2601628C (fr) *	2005-03-10	2014-05-13	Cgi Pharmaceuticals, Inc.	Amides substitues, procede pour les produire et procede pour les utiliser
WO2006124731A2 (fr)	2005-05-12	2006-11-23	Irm Llc	Composes et compositions utilise(e)s en tant qu'inhibiteurs de proteines-kinases
EP2099797B1 (fr)	2005-08-09	2010-09-29	Irm Llc	Composes et compositions utiles comme inhibiteurs de proteines kinases
WO2007027594A1 (fr)	2005-08-29	2007-03-08	Vertex Pharmaceuticals Incorporated	Pyrid-2-ones 3,5-bisubstitues utiles en tant qu'inhibiteurs de la famille tec des tyrosines kinases depourvues de la fonction recepteur
AU2006285145A1 (en)	2005-08-29	2007-03-08	Vertex Pharmaceuticals Incorporated	3,5-disubstituted pyrid-2-ones useful as inhibitors of Tec family of non-.receptor tyrosine kinases
ATE528302T1 (de)	2005-08-29	2011-10-15	Vertex Pharma	3,5-disubstituierte pyrid-2-one, die als hemmer der tec-familie von nicht-rezeptor tyrosin- kinasen nützlich sind
CN101300253B (zh) *	2005-09-09	2012-08-22	沃泰克斯药物股份有限公司	作为电压门控离子通道调控剂的二环衍生物
CA2645583A1 (fr) *	2006-03-20	2007-09-27	F. Hoffman-La Roche Ag	Procedes d'inhibition des proteines kinase btk et syk
EP2018167A4 (fr)	2006-05-15	2010-07-14	Irm Llc	Compositions et procédés utilisés en tant qu'inhibiteurs des kinases réceptrices fgf
AR063707A1 (es)	2006-09-11	2009-02-11	Cgi Pharmaceuticals Inc	Determinadas amidas sustituidas, el uso de las mismas para el tratamiento de enfermedades mediadas por la inhibicion de la actividad de btk y composiciones farmacéuticas que las comprenden.
US7838523B2 (en)	2006-09-11	2010-11-23	Cgi Pharmaceuticals, Inc.	Certain substituted amides, method of making, and method of use thereof
EP2068849A2 (fr) *	2006-09-11	2009-06-17	CGI Pharmaceuticals, Inc.	Inhibiteurs de kinase et procédés d'utilisation et d'identification des inhibiteurs de kinase
AR063706A1 (es) *	2006-09-11	2009-02-11	Cgi Pharmaceuticals Inc	Determinadas amidas sustituidas, el uso de las mismas para el tratamiento de enfermedades mediadas por la inhibicion de la actividad de btk y composiciones farmaceuticas que las comprenden.
CL2008002793A1 (es)	2007-09-20	2009-09-04	Cgi Pharmaceuticals Inc	Compuestos derivados de amidas sustituidas, inhibidores de la actividad de btk; composicion farmaceutica que los comprende; utiles en el tratamiento del cancer, trastornos oseos, enfermedades autoinmunes, entre otras
CA2701275C (fr)	2007-10-23	2016-06-21	F. Hoffmann-La Roche Ag	Inhibiteurs de kinase
NZ601700A (en) *	2008-06-24	2013-02-22	Hoffmann La Roche	5-phenyl-1H-pyridin-2-one and 6-phenyl-2H-pyridazin-3-one derivatives as inhibitors of Bruton's Tyrosine Kinase (Btk)
JP5635535B2 (ja) *	2009-01-08	2014-12-03	レスバーロジックスコーポレイション	心血管疾患の予防および治療のための化合物
US8299077B2 (en) *	2009-03-02	2012-10-30	Roche Palo Alto Llc	Inhibitors of Bruton's tyrosine kinase

2009
- 2009-06-22 PL PL09772333T patent/PL2300459T3/pl unknown
- 2009-06-22 MX MX2010013478A patent/MX2010013478A/es active IP Right Grant
- 2009-06-22 RU RU2011103234/04A patent/RU2507202C2/ru not_active IP Right Cessation
- 2009-06-22 CA CA2728683A patent/CA2728683C/fr not_active Expired - Fee Related
- 2009-06-22 SI SI200930631T patent/SI2300459T1/sl unknown
- 2009-06-22 PT PT97723332T patent/PT2300459E/pt unknown
- 2009-06-22 DK DK09772333.2T patent/DK2300459T3/da active
- 2009-06-22 HR HRP20130698AT patent/HRP20130698T1/hr unknown
- 2009-06-22 AU AU2009265813A patent/AU2009265813B2/en not_active Expired - Fee Related
- 2009-06-22 ES ES09772333T patent/ES2420854T3/es active Active
- 2009-06-22 JP JP2011515329A patent/JP5490789B2/ja not_active Expired - Fee Related
- 2009-06-22 PE PE2010001208A patent/PE20110164A1/es not_active Application Discontinuation
- 2009-06-22 KR KR1020107029738A patent/KR101320763B1/ko not_active Expired - Fee Related
- 2009-06-22 KR KR1020137016860A patent/KR101523451B1/ko not_active Expired - Fee Related
- 2009-06-22 BR BRPI0913879A patent/BRPI0913879A2/pt not_active IP Right Cessation
- 2009-06-22 CN CN200980125623.9A patent/CN102083819B/zh not_active Expired - Fee Related
- 2009-06-22 WO PCT/EP2009/057707 patent/WO2010000633A1/fr not_active Ceased
- 2009-06-22 EP EP09772333.2A patent/EP2300459B1/fr not_active Not-in-force
- 2009-06-30 TW TW098122087A patent/TWI401083B/zh not_active IP Right Cessation
- 2009-07-01 US US12/459,595 patent/US8536166B2/en not_active Expired - Fee Related
- 2009-07-01 AR ARP090102453A patent/AR072545A1/es not_active Application Discontinuation
2010
- 2010-12-02 IL IL209729A patent/IL209729A0/en unknown
- 2010-12-07 ZA ZA2010/08808A patent/ZA201008808B/en unknown
- 2010-12-29 CL CL2010001608A patent/CL2010001608A1/es unknown
2013
- 2013-08-01 CY CY20131100661T patent/CY1114223T1/el unknown

Also Published As

Publication number	Publication date
TWI401083B (zh)	2013-07-11
PT2300459E (pt)	2013-07-04
KR101523451B1 (ko)	2015-05-27
US20100004231A1 (en)	2010-01-07
IL209729A0 (en)	2011-02-28
RU2507202C2 (ru)	2014-02-20
US8536166B2 (en)	2013-09-17
KR20130093156A (ko)	2013-08-21
CN102083819B (zh)	2014-07-09
CL2010001608A1 (es)	2011-05-13
PL2300459T3 (pl)	2013-10-31
KR20110020872A (ko)	2011-03-03
DK2300459T3 (da)	2013-09-02
TW201004938A (en)	2010-02-01
EP2300459A1 (fr)	2011-03-30
AU2009265813A1 (en)	2010-01-07
JP5490789B2 (ja)	2014-05-14
WO2010000633A1 (fr)	2010-01-07
PE20110164A1 (es)	2011-03-28
AR072545A1 (es)	2010-09-08
MX2010013478A (es)	2010-12-20
SI2300459T1 (sl)	2013-07-31
RU2011103234A (ru)	2012-08-10
CN102083819A (zh)	2011-06-01
CA2728683C (fr)	2017-05-02
HRP20130698T1 (en)	2013-10-11
ZA201008808B (en)	2011-10-26
CA2728683A1 (fr)	2010-01-07
AU2009265813B2 (en)	2014-04-10
JP2011526279A (ja)	2011-10-06
EP2300459B1 (fr)	2013-05-29
KR101320763B1 (ko)	2013-10-21
CY1114223T1 (el)	2016-08-31
BRPI0913879A2 (pt)	2019-09-24

Publication	Publication Date	Title
ES2420854T3 (es)	2013-08-27	Nuevas fenilpirazinonas como inhibidores de quinasas
TWI382024B (zh)	2013-01-11	新穎之吡啶酮及嗒酮
ES2461494T3 (es)	2014-05-20	Nuevas fenilimidazopirazinas
US8822457B2 (en)	2014-09-02	Inhibitors of bruton's tyrosine kinase
US8318719B2 (en)	2012-11-27	Inhibitors of Bruton's tyrosine kinase
JP5318952B2 (ja)	2013-10-16	新規なフェニル−イミダゾピリジン類及びピリダジン類
ES2499017T3 (es)	2014-09-26	Nuevos inhibidores de quinasa
KR20150054994A (ko)	2015-05-20	브루톤 티로신 키나아제의 억제제
CN104837837B (zh)	2017-04-05	作为布鲁顿氏酪氨酸激酶抑制剂的噻唑衍生物